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We just bought a 2-story house. I need pointers on what to do to make AC/Heat more efficient. Do I close downstairs vents, close doors upstairs, what about crawlspace vents? Upstairs master bedroom does have ceiling fan which we run during the night.

Is there a problem with the way it's running now? I wouldn't think that someone would put a supply in a crawl space, that would just invite critters to move in. You should have an HVAC contractor do a PM just to make sure everything is working OK, both Heat and AC

Closing off registers is generally not a good idea because it is very common for houses to have duct systems that are already only marginally large enough to handle the airflow from equipment that is often over-sized for the home's needs.

When you start closing registers, you restrict the airflow further, thereby reducing the efficiency of the equipment. This is especially a concern for A/C, since cooling capacity and efficiency are directly related to adequate airflow. A 3-ton unit can perform like a 2-ton unit if airflow is restricted.

Crawlspace vents: (assuming you mean vents to the outside) depending on the climate, it is generally good to open the vents in summer, but close them in winter.

We just bought a 2-story house. I need pointers on what to do to make AC/Heat more efficient. Do I close downstairs vents, close doors upstairs, what about crawlspace vents? Upstairs master bedroom does have ceiling fan which we run during the night.

Depending on a number of factors, I would consider zoning.
Your current thermostat is (probably) downstairs, with zoning you would also have one upstairs.
Each floor can have it's own setting depending on day or night.